Atrial fibrillation (AF) is a well-established independent risk factor for stroke. We examined cerebral blood flow augmentation in the treatment of acute ischemic stroke (AIS) in patients with AF by performing secondary analysis of data from the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial, a randomized controlled trial evaluating NeuroFlo treatment in stroke patients within 14 hours of symptom onset. We report subgroup analyses of outcomes in SENTIS patients with a history or new diagnosis of AF. Among patients with AF, those treated with NeuroFlo demonstrated significant improvement over those not treated for multiple end points: global efficacy end point (P = .030), modified Rankin Scale (mRS) score 0-2 versus 3-6 (P = .029), and stroke-related mortality (P = .015). There was a significant improvement in global end point for those aged 60 years or older (P = .042) and 80 years or older (P = .017), with a trend toward improvement for age 70 years or older (P = .055), and significant improvement in those who achieved good outcomes (mRS score 0-2 versus 3-6) at age 60 years or older (P - .038), 70 years or older (P - .022), and 80 years or older (P - .008). NeuroFlo treatment in stroke patients with AF resulted in significantly better outcomes compared with nontreated patients with AF. Collateral flow recruitment, maintenance of cerebral blood flow around stroke core, and improvement of penumbral blood flow are potential mechanisms for these improved outcomes. NeuroFlo may represent a valid therapeutic option for patients with AF and AIS, and therefore, future trials of the device are warranted.